This project explores the nature of antibody responses to CD4 and the possible application of such antibodies as an idiotypic vaccines for AIDS. In order to derive appropriate anti-CD4 antibodies for vaccine studies, responses to CD4 must be better understood. Specific projects: 1) We have studied the genetic control of antibody responses in mice to human CD4. Mice were immunized with MOLT-4, a CD4-bearing human T cell line. Sera were tested for three parameters: overall antibody to the T cells used, antibody to rCD4, and antibody to rCD4, and antibody to the gp120 binding site on CD4 as tested by inhibition of gp120 binding. Results indicate that while all strains made similar responses to T cells, A.TL mice were low responders to the gp120 site while A.TH and A.SW mice were high responders. This indicates MHC-linked Ir gene control of responses to the site. It also indicates that in this response to an antigen presented as a cell surface structure, intermolecular carrier effects do not dominate because the Ir gene defect is specific to this site. 2) We have derived anti-CD4 mAbs by direct immunization with CD4+ T cells or with CD4-IgG. These antibodies will be tested for site specificity. 3) We have derived a panel of antibodies to gp120, and are defining the sites they recognize. These mAbs will be evaluated for use in studies of idiotypic manipulation as a potential vaccine for AIDS.